The Liver As A Storage Organ Flashcards
What are the functions of the liver?
Carbohydrate metabolism
Fat metabolism
Protein metabolism
Hormone metabolism
Toxin/Drug metabolism and excretion
Storage
Bilirubin metabolism and excretion
Iron metabolism
Dietary iron is absorbed into the blood plasma by a transferrin
The iron is depositied in a number of different places, including myoglobin in muscles, iron in Hb in red blood ells, or stored in liver and reticuloendothelial macrophages
Ferritin
Large spherical protein consisting of 24 noncovalently linked subunits
Subunits form a shell surrounding a central core.
Core contains up to 5000 atoms of iron.
Ferritin found in the cytoplasm of cells but can also be found in the serum.
Concentration of ferritin is directly proportional to the total iron stores in the body
Ferritin excess
Can be due to excess iron storage disorders
Examples on slide 6
Can be due to non iron overload:
Liver disease
Some malignancies
Significant tissue destruction
Acute phase response (a protein that increases in response to acute condition):
-Inflammation
-Infection
-Autoimmune disorders
These lead to ferritin also rising
Ferritin deficiency
The only known cause of a low ferritin is iron deficiency
This can result in anaemia
-Ferritin less than 20 µg/L indicates depletion
-Ferritin less than 12 µg/L suggests a complete absence of stored iron.
Vitamins
Usually vitamins are provided in the diet.
Characteristic disorders when someone is vitamin deficient.
Recommended daily allowance (RDA)
Adequate intake (AI) where no evidence to determine RDA
Vitamins act as:
-Gene activators
-Free-radical scavengers
Coenzymes or cofactors in metabolic reactions
Excessive vitamin ingestion can result in toxicity
Water soluble vitamins
B and C
Fat soluble vitamins
A, D, E and K
Difference between fat soluble and water soluble vitamins
Water soluble vitamins pass more readily through the body, therefore, require more regular intake than fat soluble vitamins
Vitamin A (Retinoids)
Vertebrates ingest retinal directly from meat or produce retinal from carotenes (vegetables)
Requirements: 0.6 mg/day in men, 0.7 mg/day in women
Functions of Vitamin A
Vision:
-Used to form rhodopsin in the rod cells in the retina.
Reproduction:
-Spermatogenesis in male
-Prevention of foetal resorption of female
Growth
Stabilisation of cellular membranes
Vitamin A Deficiency
Rare in affluent countries as vitamin A levels drop only when liver stores are severely depleted.
Deficiency may occur due to fat malabsorption
Clinical Features:
-Night blindness
-Xeropthalmia
-Blindness
Vitamin A excess
Acute:
-Abdominal pain, nausea and vomiting
-Severe headaches, dizziness, sluggishness and irritability
-Desquamation of the skin
Chronic:
-Joint and bone pain
-Hair loss, dryness of the lips
-Anorexia
-Weight loss and hepatomegaly
Carotenemia:
-Reversible yellowing of the skin
-Does not cause toxicity
Functions of Vitamin D
Increased intestinal absorption of calcium
Resorption and formation of bone
Reduced renal excretion of calcium
Vitamin D deficiency
Demineralisation of bone:
-Rickets in children
-Osteomalacia in adults
Sources of Vitamin D
Fish and meat
Sunlight (7-dehydrocholestral)
25- hydroxyvitamin D3 is active version of vitamin D
1,25-dihydroxyvitamin D3 stored versions- maintains calcium balance in the body
Vitamin E stored in
Non-adipose cells such as liver and plasma – labile (widely available for use) and fixed pool (mobilised slowly)
Adipose cells – fixed pool
Function of Vitamin E
Important antioxidant
Vitamin E requirements
4 mg/day in men
3 mg/day in women
Causes of Vitamin E deficiency
Fat malabsorption (e.g. cystic fibrosis)
Premature infants
Rare congenital defects in fat metabolism e.g. abetalipoproteinaemia.
Vitamin E excess
Relatively safe
Vitamin K sources
Vitamin K is rapidly taken up by the liver but then is transferred to very low-density lipoproteins and low density lipoproteins which carry it into the plasma.
Sources:
Vitamin K1 (phylloquinone)
-Synthesized by plants and present in food
Vitamin K2 (menaquinone)
-Synthesized in humans by intestinal bacteria
Synthetic vitamin K’s:
-K3 (menadione)
-K4 (menadiol)
Functions of Vitamin K
Vitamin K is responsible for the activation of some blood clotting factors.
Necessary for liver synthesis of plasma clotting factors II, VII, IX and X.
Can be assessed by measuring prothrombin tim
Vitamin K deficiency
Haemorrhagic disease of the newborn:
-Vitamin K injection given to newborn babies
Rare in adults, unless on warfarin
Vitamin K excess
K1 is relatively safe
Synthetic forms are more toxic
Can result in oxidative damage, red cell fragility and formation of methaemoglobin.
Vitamin C is found in
Fresh fruit and vegetables
Requirement of Vitamin C
40mg/day
Functions of vitamin C
Collagen synthesis
Antioxidant
Iron absorption
Deficiency of Vitamin C
Scurvy- easy bruising and bleeding, hair loss, teeth and gum disease
Treatment with vitamin C improves systems quickly
Excess vitamin C
Doses > 1g/day can cause GI side effects
No evidence that increased vitamin C reduces the incidence or duration of colds.
Vitamin B12 (Cobalamins) has 2 active forms
Methylcobalamin
5-deoxyadenosylcobalamin
Vitamin B12 (Cobalamins)
Released from food by acid and enzymes in the stomach
Binds to R protein to protect it from stomach acid
Released from R proteins by pancreatic polypeptide.
Intrinsic factor (IF) produced by the stomach needed for absorption.
IF-B12 complex absorbed in the terminal ileum.
B12 is stored in the liver.
Stored in
Fish, eggs, milk, meat
Causes of vitamin B12 deficiency
Pernicious anaemia – autoimmune destruction of IF-producing cells in stomach.
Malabsorption – lack of stomach acid, pancreatic disease, small bowel disease.
Veganism
Symptoms of Vitamin B12 deficiency
Macrocytic anaemia
Peripheral neuropathy in prolonged deficiency
Folate
Folate is found in may foods fortified with folic acid.
Individuals have higher requirements in pregnancy.
Functions of folate
Functions as a coenzyme in methylation reactions, DNA synthesis, synthesis of methionine from homocysteine.
Causes of folate deficiency
Malabsorption
Drugs that interfere with folic acid metabolism (anticonvulsants, methotrexate)
Disease states that increase cell turnover (e.g. leukaemia, haemolytic anaemia, psoriasis)
Symptoms of folate deficiency
High homocysteine levels
Macrocytic anaemia
Foetal development abnormalities (neural tube defects)
Clotting factors
Intrinsic pathway activated by contact.
Extrinsic pathway activated by FVII coming in contact with tissue factor.
Initiates a cascade which ultimately results in fibrin clot formation.
Clotting factors produced in the liver
I (Fibrinogen)
II (Prothrombin)
IV
V
VI
VII
The performance of the clotting pathways can be measured using:
Prothrombin time (PT) (extrinsic pathway)
International normalised ratio (INR)
Activated partial thromboplastin time (aPTT) (intrinsic pathway)
Prolonged PT
A prolonged PT may indicate a deficiency in the synthetic capacity of the liver.
Prolonged PT is not specific for liver disease:
-DIC
-Severe GI bleeding
-Some drugs
-Vitamin K deficiency
